First Online: 01 July 2009Received: 27 January 2009Accepted: 01 July 2009

Abstract

BackgroundGender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development.To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells PBMC in patients with rare defined -disorders of sex development- DSD, e.g., 46, XY-females due to defective androgen biosynthesis compared to normal 46, XY-males and 46, XX-females.

ResultsA discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia.However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels.Consequently, the architecture of the transcriptional PBMC-sexes- was either male, female or even -intersex- with a discordant alignment of the DSD individuals- genetic and hormonal sex signatures.

ConclusionA significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization.Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions.

AbbreviationsDSDdisorders of sex development

CAHcongenital adrenal hyperplasia

SMDStanford Microarray Database

SAMSignificance Analysis of Microarrays

GSEAGene Set Enrichment Analysis

PANTHERProtein ANalysis THrough Evolutionary Relationships.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-10-292 contains supplementary material, which is available to authorized users.